87.23 Sirolimus Therapy for Chylous Ascites Associated with Lymphatic Anomalies in Children

S. Creden1,2, A. Espinoza1,2, O. Olutoye1,2, T. Nack1,2, Y. D. Sevilmis1,2, I. Iacobas1,3, K. Rialon1,2  1Baylor College Of Medicine, General Surgery, Houston, TX, USA 2Texas Children’s Hospital, Pediatric Surgery, Houston, TX, USA 3Texas Children’s Hospital, Pediatric Hematology And Oncology, Houston, TX, USA

Introduction:
Lymphatic anomalies (LAs) are a highly variable clinical entity, including both discrete malformations and generalized anomalies. If a LA involves central collecting channels, chylous ascites (CA) may develop. Morbidity may be secondary to loss of intravascular fluid, chyle, and protein; mass effect; or frequent infections. Procedural interventions include percutaneous drainage, shunt placement, and/or surgical resection. Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor thought to regulate angiogenesis and cell growth, has garnered attention as a treatment modality for LAs. The effect of sirolimus on CA in children has yet to be well characterized.

Methods:
A retrospective chart review was performed at single tertiary referral center with a multidisciplinary Vascular Anomalies Center from 2010 to 2022 of all patients under 18 years of age presenting with CA. Sirolimus was administered according to institutional treatment guidelines.

Results:
Sixteen patients were identified to have a LA with CA. Eleven patients possessed a generalized LA. Other diagnoses include GI lymphangiectasia with protein losing enteropathy, and non-immune hydrops. Three patients (19%) were noted to be premature. The median age at diagnosis was 5.5 months (interquartile range [IQR] 1 month – 36 months). The median age at sirolimus initiation was 8 months (IQR 1 month – 6 years). The most common medical therapies employed prior to initiating sirolimus were furosemide in 7 (44%) and octreotide in 7 (44%) patients. Nine patients required peritoneal drainage prior to initiating sirolimus. Following initiation of sirolimus, 5 patients (31%) required temporary interruption of administration due to infectious events. Of those 5, none survived (100% mortality). This is in contrast to 5 deaths among those with no complications of sirolimus treatment (5/11 = 45%). Two patients underwent lymphaticovenous bypass surgery, but only 1 was successful. Two patients underwent placement of a Denver Shunt. Following initiation of sirolimus, 8 (50%) showed stabilization or decrease in drain output, and 2 (22%) patients’ drains were removed. In the 5 patients that received sirolimus alone with no surgical intervention, 2 (40%) recovered; the other 3 (60%) did not survive. In those with chromosomal abnormalities (n=3), none survived. Of the 16 patients, there was a 63% mortality rate. The median age at initiation for surviving patients was 5 years, compared to 2 months for those that did not survive.

Conclusion:
In this medically complex pediatric population, over half of patients treated with sirolimus showed improvement. Mortality remains high in the overall population, particularly for those with a chromosomal abnormality, those that developed chylous ascites and required treatment in infancy, and those that required interruptions in the sirolimus administration due to infections.